全文获取类型
收费全文 | 1120篇 |
免费 | 65篇 |
国内免费 | 2篇 |
出版年
2023年 | 11篇 |
2022年 | 42篇 |
2021年 | 78篇 |
2020年 | 62篇 |
2019年 | 76篇 |
2018年 | 52篇 |
2017年 | 37篇 |
2016年 | 35篇 |
2015年 | 63篇 |
2014年 | 70篇 |
2013年 | 91篇 |
2012年 | 80篇 |
2011年 | 82篇 |
2010年 | 38篇 |
2009年 | 37篇 |
2008年 | 40篇 |
2007年 | 31篇 |
2006年 | 27篇 |
2005年 | 23篇 |
2004年 | 22篇 |
2003年 | 20篇 |
2002年 | 15篇 |
2001年 | 6篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1995年 | 2篇 |
1994年 | 7篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 10篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 6篇 |
1972年 | 4篇 |
排序方式: 共有1187条查询结果,搜索用时 832 毫秒
71.
Habibollah Faraji Mohammad Ramezani Baratali Mashkani Hamid R. Sadeghnia Hamid M. Benhangi Saeed Hosseini Teshnizi Fatemeh Soltani 《Biotechnology progress》2019,35(4):e2819
Staphylokinase (SAK) is a promising thrombolytic agent for the treatment of patients suffering from blood-clotting disorders. To increase the potency of SAK and to minimize vessel reocclusion, a new construct bearing SAK motif fused to tsetse thrombin inhibitor (TTI) via a 20-amino acid linker with 2 RGD (2 × arginine-glycine-aspartic acid inhibiting platelet aggregation via attachment to integrin receptors of platelet) was codon optimized and expressed comparatively in Pichia pastoris GS115 as a Mut+ strain and KM71H as a Muts strain. Fusion protein was optimized in terms of best expression condition and fibrinolytic activity and compared with the rSAK. Expression level of the designed construct reached up to 175 mg/L of the culture medium after 72-hr stimulation with 2.5% methanol and remained steady for 3–4 days. The highest expression was obtained at the range of 2–3% methanol. The SAK-2RGD-TT (relative activity >82%) was more active at 25–37 °C than rSAK (relative activity of 93%). Further, it showed relative activity >80% at pH ranges of 7–9. Western blot analysis showed two bands of nearly 27 and 24 kDa at ratio of 5 to 3, respectively. The specific fibrinolytic activity of the SAK-2RGD-TTI was measured as 8,269 U/mg, and 19,616 U/mg for the nonpurified and purified proteins, respectively. Deglycosylation by using tunicamycin in culture medium resulted in higher fibrinolytic activity of SAK-2RGD-TTI (2.2 fold). Consequently, compared to the rSAK, at the same equimolar proportion, addition of RGD and TTI fragments could increase fibrinolytic activity. Also, P. pastoris can be considered as an efficient host for overexpression of the soluble SAK-2RGD-TTI with high activity without requiring a complicated purification procedure. 相似文献
72.
Handisurya A Gilch S Winter D Shafti-Keramat S Maurer D Schätzl HM Kirnbauer R 《The FEBS journal》2007,274(7):1747-1758
Prion diseases are fatal neurodegenerative disorders caused by proteinaceous infectious pathogens termed prions (PrP(Sc)). To date, there is no prophylaxis or therapy available for these transmissible encephalopathies. Passive immunization with monclonal antibodies recognizing the normal host-encoded prion protein (PrP(C)) has been reported to abolish PrP(Sc) infectivity and to delay onset of disease. Because of established immunologic tolerance against the widely expressed PrP(C), active immunization appears to be difficult to achieve. To overcome this limitation, papillomavirus-like particles were generated that display a nine amino acid B-cell epitope, DWEDRYYRE, of the murine/rat prion protein in an immunogenic capsid surface loop, by insertion into the L1 major capsid protein of bovine papillomavirus type 1. The PrP peptide was selected on the basis of its previously suggested central role in prion pathogenesis. Immunization with PrP-virus-like particles induced high-titer antibodies to PrP in rabbit and in rat, without inducing overt adverse effects. As determined by peptide-specific ELISA, rabbit immune sera recognized the inserted murine/rat epitope and also cross-reacted with the homologous rabbit/human epitope differing in one amino acid residue. In contrast, rat immune sera recognized the murine/rat peptide only. Sera of both species reacted with PrP(C) in its native conformation in mouse brain and on rat pheochromocytoma cells, as determined by immunoprecipitation and fluorescence-activated cell sorting analysis. Importantly, rabbit anti-PrP serum contained high-affinity antibody that inhibited de novo synthesis of PrP(Sc) in prion-infected cells. If also effective in vivo, PrP-virus-like particle vaccination opens a unique possibility for immunologic prevention of currently fatal and incurable prion-mediated diseases. 相似文献
73.
Cluster Computing - HPC or super-computing clusters are designed for executing computationally intensive operations that typically involve large scale I/O operations. This most commonly involves... 相似文献
74.
Anwar Fathollahi Saeed Aslani Ahmadreza Jamshidi Mahdi Mahmoudi 《Journal of cellular physiology》2019,234(8):12309-12324
Osteoarthritis (OA) is the most common type of arthritis and no longer is considered as an absolute consequence of joint mechanical use (wear and tear); rather recent data demonstrate the pivotal role of inflammatory mediators in the development and progression of this disease. This multifactorial disease results from several environmental and inherited factors. Genetic cannot solely explain all the contribution share of inheritance and, this way, it is speculated that epigenetics can play a role, too. Moreover, environmental factors can induce local epigenetic changes. The epigenetic contribution to OA pathogenesis occurs at all of its levels, DNA methylation, histone modification, microRNA, and long noncoding RNA. In fact, during early phases of OA pathogenesis, environmental factors employ epigenetic mechanisms to provide a positive feedback for the OA-related pathogenic mechanisms and pathways with an ultimate outcome of a well-established clinical OA. These epigenetic changes stay during clinical disease and prevent the body natural healing and regenerative processes to work properly, resulting in an incurable disease condition. In this review article, we aimed to have an overview on the studies performed with regard to understanding the role of epigenetics in the etiopathogenesis of OA and highlighted the importance of such kind of regulatory mechanisms within this context. 相似文献
75.
Elaheh Esmaeili Masoud Soleimani Mohammad Adel Ghiass Shadie Hatamie Saeed Vakilian Mahsa Soufi Zomorrod Negar Sadeghzadeh Manouchehr Vossoughi Simzar Hosseinzadeh 《Journal of cellular physiology》2019,234(8):13617-13628
While the differentiation factors have been widely used to differentiate mesenchymal stem cells (MSCs) into various cell types, they can cause harm at the same time. Therefore, it is beneficial to propose methods to differentiate MSCs without factors. Herein, magnetoelectric (ME) nanofibers were synthesized as the scaffold for the growth of MSCs and their differentiation into neural cells without factors. This nanocomposite takes the advantage of the synergies of the magnetostrictive filler, CoFe2O 4 nanoparticles (CFO), and piezoelectric polymer, polyvinylidene difluoride (PVDF). Graphene oxide nanosheets were decorated with CFO nanoparticles for a proper dispersion in the polymer through a hydrothermal process. After that, the piezoelectric PVDF polymer, which contained the magnetic nanoparticles, underwent the electrospun process to form ME nanofibers, the ME property of which has the potential to be used in areas such as tissue engineering, biosensors, and actuators. 相似文献
76.
Vahid Hosseini Christian Dani Mohammad Hossein Geranmayeh Fatemeh Mohammadzadeh Saeed Nazari Soltan Ahmad Masoud Darabi 《Journal of cellular physiology》2019,234(6):8040-8054
The Wnt signaling pathway consists of various downstream target proteins that have substantial roles in mammalian cell proliferation, differentiation, and development. Its aberrant activity can lead to uncontrolled proliferation and tumorigenesis. The posttranslational connection of fatty acyl chains to Wnt proteins provides the unique capacity for regulation of Wnt activity. In spite of the past belief that Wnt molecules are subject to dual acylation, it has been shown that these proteins have only one acylation site and undergo monounsaturated fatty acylation. The Wnt monounsaturated fatty acyl chain is more than just a hydrophobic coating and appears to be critical for Wnt signaling, transport, and receptor activation. Here, we provide an overview of recent findings in Wnt monounsaturated fatty acylation and the mechanism by which this lipid moiety regulates Wnt activity from the site of production to its receptor interactions. 相似文献
77.
78.
79.
Kaveh Baghaei Samaneh Tokhanbigli Hamid Asadzadeh Saeed Nmaki Mohammad Reza Zali Seyed Mahmoud Hashemi 《Journal of cellular physiology》2019,234(7):9910-9926
Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy. However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models. In this review, we consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell-free therapeutic approach in gastrointestinal diseases like IBD, gastric cancer, and colon cancer. Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell-derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials. Therefore, all these striking functions described for secretome implies the importance of these biocarriers. 相似文献
80.
Omid Reza Tamtaji Moein Mobini Russel J. Reiter Abolfazl Azami Mohammad Saeed Gholami Zatollah Asemi 《Journal of cellular physiology》2019,234(6):7788-7795
Toll-like receptors (TLRs) are crucial activators of inflammatory responses, they are considered immune receptors. TLRs are of fundamental importance in the pathophysiology of disorders related to inflammation including neurodegenerative diseases and cancer. Melatonin is a beneficial agent in the treatment of inflammatory and immune disorders. Melatonin is potent anti-inflammatory hormone that regulates various molecular pathways. Withal, limited studies have evaluated the inhibitory role of melatonin on TLRs. This review summarizes the current knowledge related to the effects of melatonin on TLRs in some common inflammatory and immunity disorders. 相似文献